Electrophysiological analysis of vulnerability to experimental ischemia in neonatal rat spinal ventral horn neurons

To clarify the vulnerability of spinal motoneurons to excitotoxicity, we analyzed the agonal current induced by experimental ischemia in ventral lamina IX neurons of spinal cord slices from neonatal rats by using whole-cell patch-clamp. Ischemia was simulated in vitro by oxygen/glucose deprivation. Superfusion with ischemia-simulating medium elicited an agonal inward current, which was initially slow and then became rapid. We compared 8-, 9-, 10-, 11-, and 12-day postnatal rats and found age-dependent shortening of the latency of the rapid inward current. Furthermore, the membrane capacitance (Cm) and resting membrane potential (RMP) of the lamina IX neurons demonstrated significant negative correlations with the latency of the rapid inward current. Logistic regression analysis showed that postnatal age, Cm, and RMP were independent contributing factors to ischemic vulnerability. These results suggest that not only cell volume and ionic balance but also early postnatal maturation of the intracellular environment is vital for developing vulnerability to excitotoxicity.